Originator
Betaloc,Astra,UK,1975
Uses
Antiadrenergic (β-receptor).
Uses
Metoprolol is a β-adrenergic blocking antihypertensive and antianginal agent; to treat raised blood pressure; to prevent attacks of angina (pain
from an inadequate oxygen supply to the heart); after a heart attack to prevent further damage to the heart muscle; treatment of some
disturbances of heart rhythm; used to help prevent attacks of migraine; in ophthalmic preparations; treatment of myocardial infarcts.
Uses
Metoprolol is used in moderate hypertension, serious conditions of myocardial infarction, for preventing death of cardiovascular tissue, in angina, tachycardia, extrasystole, and
for secondary prophylaxis after a heart attack.
Definition
ChEBI: Metoprolol is a propanolamine that is 1-(propan-2-ylamino)propan-2-ol substituted by a 4-(2-methoxyethyl)phenoxy group at position 1. It has a role as a beta-adrenergic antagonist, an antihypertensive agent, a xenobiotic, an environmental contaminant and a geroprotector. It is a propanolamine, an aromatic ether, a secondary alcohol and a secondary amino compound.
Manufacturing Process
The starting material 1,2-epoxy-3-[p-(β-methoxyethyl)phenoxy]-propane was
obtained from p-(β-methoxyethyl)-phenol which was reacted with
epichlorohydrin whereafter the reaction product was distilled at 118°C to
128°C at a pressure of 0.35mm Hg.
1,2-Epoxy-3-[p-(β-methoxyethyl)-phenoxy]-propane (16.7g) was dissolved in
50 ml isopropanol and mixed with 20 ml isopropylamine. The mixture was
heated in an autoclave on boiling water-bath overnight, whereafter it was
evaporated and the remainder dissolved in 2 N HCI. The solution was
extracted first with ether and thereafter with methylene chloride. After
evaporating the methylene chloride phase, the hydrochloride of 1-
isopropylamino-3-[p(β-methoxyethyl)-phenoxy] -propanol-2 was obtained
which, after recrystallization from ethyl acetate, weighed 10.4 g. Melting point
83°C. Equivalent weight: found 304.0, calculated 303.8.
The hydrochloride is then converted to the tartrate.
Brand name
Lopressor (Novartis).
Therapeutic Function
Beta-adrenergic blocker
Mechanism of action
Unlike propranolol, which blocks both β1 and β2-adrenoreceptors, metroprolol exhibits
cardioselective action, i.e. in therapeutic doses, it blocks β1-adrenoreceptors with insignificant
effects on β2-adrenoreceptors.
Synthesis
Metoprolol, 1-(iso-propylamino)-3-[4??(2-methoxyethyl)phenoxy]-2-
propanol (12.1.5), is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorhydride in the presence of a base, isolating 1,2-epoxy-3-[4??(2-methoxyethyl)phenoxy]
propane (12.1.4), the subsequent reaction of which, analogous to that described before,
with iso-propylamine, gives an opening of the epoxide ring and leads to the formation of
metoprolol (12.1.5) [7,8].
Metabolism
The pharmacokinetic profile of metoprolol (Lopressor)
is similar to that of propranolol. Metoprolol is readily
and rapidly absorbed after oral administration and is
subject to a significant amount of first-pass metabolism
by the liver. Curiously, the duration of metoprolol’s action
is longer than one would predict from its plasma
half-life, which ranges from 0.5 to 2.5 hours. The degree
of binding of metoprolol to plasma proteins is modest
(10%). The extensive distribution of metoprolol to the
lungs and kidney is typical of a moderately lipophilic
drug. Metoprolol undergoes considerable metabolism;only 3 to 10% of an administered dose is recovered as
unchanged drug.The metabolites are essentially inactive
as -receptor blocking agents and are eliminated primarily
by renal excretion. Small amounts of the drug are
present in the feces.
